Temperature effects on neuronal membrane potentials and inward currents in rat hypothalamic tissue slices

Abstract

Preoptic-anterior hypothalamic (PO/AH) neurones sense and regulate body temperature. Although controversial, it has been postulated that warm-induced depolarization determines neuronal thermosensitivity. Supporting this hypothesis, recent studies suggest that temperature-sensitive cationic channels (e.g. vanilloid receptor TRP channels) constitute the underlying mechanism of neuronal thermosensitivity. Moreover, earlier studies indicated that PO/AH neuronal warm sensitivity is due to depolarizing sodium currents that are sensitive to tetrodotoxin (TTX). To test these possibilities, intracellular recordings were made in rat hypothalamic tissue slices. Thermal effects on membrane potentials and currents were compared in PO/AH warm-sensitive, temperature-insensitive and silent neurones. All three types of neurones displayed slight depolarization during warming and hyperpolarization during cooling. There were no significant differences in membrane potential thermosensitivity for the different neuronal types. Voltage clamp recordings (at −92 mV) measured the thermal effects on persistent inward cationic currents. In all neurones, resting holding currents decreased during cooling and increased during warming, and there was no correlation between firing rate thermosensitivity and current thermosensitivity. To determine the thermosensitive contribution of persistent, TTX-sensitive currents, voltage clamp recordings were conducted in the presence of 0.5 µM TTX. TTX decreased the current thermosensitivity in most neurones, but there were no resulting differences between the different neuronal types. The present study found no evidence of a resting ionic current that is unique to warm-sensitive neurones. This supports studies suggesting that neuronal thermosensitivity is controlled, not by resting currents, but rather by currents that determine rapid changes in membrane potential between successive action potentials.

G-Protein-Gated Potassium (GIRK) Channels Containing the GIRK2 Subunit Are Control Hubs for Pharmacologically Induced Hypothermic Responses

“…Although the basic mechanisms of neuronal thermosensitivity remain unresolved, most researchers in this field agree that the firing rate of warm-sensitive neurons in the preoptic-anterior hypothalamus is important in sensing changes in core temperature and controlling both physiological and behavioral thermoregulatory responses (Zhao and Boulant, 2005). Warming of the body increases the firing rate of these neurons.…”

The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not

“…Furthermore, TRPV1 channels are probably not involved in POA mechanisms of thermosensitivity. Indeed, when POA neurons are exposed to different temperatures, the effects evoked (changes in brief ionic currents of the depolarizing prepotential) are different from the TRP-mediated effects (changes in the resting membrane potential) (Zhao and Boulant, 2005;Boulant, 2006), even though some authors think that mechanisms of central thermosensitivity may be compatible with participation of neuronal thermo-TRP channels (Kobayashi et al, 2006). Moreover, when ruthenium red, a nonselective TRPV1 antagonist, was applied to MPO slices in vitro, it did not reduce the thermosensitivity of warm-sensitive MPO neurons (Unger et al, 2008).…”

Heat Stroke

“…Thermal signals in the form of action potentials are generated within skin and core thermal receptors including warm-and cold-sensitive neurons within the POAH that change their firing rate in response to warming and cooling, respectively (53). Thermosensitivity of warm-sensitive neurons is determined by the rate of spontaneous depolarization between successive action potentials whereas sensitivity of cold-sensitive neurons is thought to be due to inhibitory input from nearby warm-sensitive neurons (417). A unique morphological characteristic of POAH thermosensitive neurons is the horizontal orientation of their dendrites toward other brain regions (e.g., third ventricle and medial forebrain bundle) that receive thermal signals from peripheral sites (136).…”